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US5958781A - Methods and reagents for cyanide-free determination of hemoglobin and leukocytes in whole blood - Google Patents

Methods and reagents for cyanide-free determination of hemoglobin and leukocytes in whole blood Download PDF

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US5958781A
US5958781A US08/863,827 US86382797A US5958781A US 5958781 A US5958781 A US 5958781A US 86382797 A US86382797 A US 86382797A US 5958781 A US5958781 A US 5958781A
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lyse
wbc
chloride
multipurpose
whole blood
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Show-Chu Wong
Sylvia Khoo
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Nortel Networks Ltd
Abbott Laboratories
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/72—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood pigments, e.g. haemoglobin, bilirubin or other porphyrins; involving occult blood
    • G01N33/721—Haemoglobin
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5094—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for blood cell populations
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S435/00—Chemistry: molecular biology and microbiology
    • Y10S435/962—Prevention or removal of interfering materials or reactants or other treatment to enhance results, e.g. determining or preventing nonspecific binding
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S435/00—Chemistry: molecular biology and microbiology
    • Y10S435/967—Standards, controls, materials, e.g. validation studies, buffer systems
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S436/00—Chemistry: analytical and immunological testing
    • Y10S436/826—Additives, e.g. buffers, diluents, preservatives
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/10—Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/10—Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
    • Y10T436/101666—Particle count or volume standard or control [e.g., platelet count standards, etc.]
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/10—Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
    • Y10T436/105831—Protein or peptide standard or control [e.g., hemoglobin, etc.]
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/10—Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
    • Y10T436/107497—Preparation composition [e.g., lysing or precipitation, etc.]
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/10—Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
    • Y10T436/108331—Preservative, buffer, anticoagulant or diluent
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/11—Automated chemical analysis
    • Y10T436/115831—Condition or time responsive
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    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
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    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
    • Y10T436/25125—Digestion or removing interfering materials
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
    • Y10T436/2525—Stabilizing or preserving

Definitions

  • the present invention is directed to methods and reagents which are useful in the determination of hemoglobin and leukocytes in whole blood samples. More particularly, the present invention relates to cyanide-free reagents for use in the rapid formation of a stable and detectable chromogen which is indicative of the amount of hemoglobin present in a whole blood sample by conventional methodology. In addition, the present invention is suitable for leukocyte determinations as well as for hemoglobin measurements.
  • the reagents and methods are particularly suited to application to automated hematology instruments, especially instruments which utilize the same aliquot of whole blood sample with a lyse reagent adapted for both hemoglobin and leukocyte determinations.
  • WBC white blood cell
  • Hb hemoglobin
  • the throughput of current automated hematology instruments requires the use of methods and reagents exhibiting rapid reactions rates.
  • the hemoglobin sample turnover rate of an Abbott Laboratories Cell-Dyn® 3000 instrument is approximately twelve (12) seconds.
  • Abbott Laboratories Cell-Dyn® 1600 and 3500 instrument systems take approximately twenty-four (24) seconds for hemoglobin determinations.
  • most of these instruments call for the same blood sample aliquot and reagent systems to be used for both the white blood cell size and population determinations, as well as the concentration of hemoglobin in the erythrocytes.
  • Current hematology analyzers often utilize the same dilution and reaction mixtures of whole blood and reagent for both hemoglobin determination and white blood cell counting and sizing.
  • the "standard" lysingfhemoglobin reagent typically contains ingredients to properly lyse the erythrocytes to permit accurate leukocyte counting, and a cyanide containing compound for the formation of a stable chromogen (cyanmethemoglobin) to enable precise colorometric analysis of the hemoglobin content in the erythrocytes. Therefore, in order for a new lysing reagent to be practical, it must be easily adopted for use in existing automated and semi-automated hematology instruments without alteration of either the instrumentation or the performed methodologies. Consequently, there are many significant requirements which must be met by a cyanide-free lysing reagent. Some of these are:
  • the chromogen produced should have maximum absorbance between 530 nm and 550 nm, which is the optimal absorbance range for cyanmethemoglobin of the majority of current, automated methodologies.
  • the chromogen produced should not only be quick to form, but also be fairly stable for a period of at least five minutes to provide good, reproducible results in automated or semi-automatic methods of hemoglobin and leukocyte determinations.
  • the lysing reagent should not interfere with the formation of the hemoglobin chromogen and cannot adversely affect the leukocytes' stability during leukocyte sizing and counting procedures.
  • Methods are provided for making Hb and WBC determinations and compositions comprising diluting a whole blood sample with a diluent and mixing the whole blood sample/diluent with an aqueous lyse reagent comprising from about 0.1 to about 20% by weight of at least one quartenary ammonium salt selected from the group consisting of: tetradecyltrimethyl ammonium bromide (TTAB), dodecyltrimethyl ammonium chloride, cetyltrimethyl ammonium bromide, hexadecyltrimethyl ammonium bromide, benzalkonium chloride, cetylpyridium chloride and from about 0.1 to about 15% weight of hydroxylamine salts selected from the group consisting of: hydrochloride, sulfate, phosphate and other acid salts.
  • TTAB tetradecyltrimethyl ammonium bromide
  • TTAB tetradecyltrimethyl ammonium bromide
  • compositions are provided of multipurpose cyanide-free lyse reagents which can be utilized in various instrumentations.
  • FIG. 1 is a spectrum showing absorbance curves for normal whole blood samples treated with various chromogen-forming reagents, including the reagent of the present invention, which demonstrates that the lysing reagent of the present invention has an absorbance range in the same range as exhibited by presently available lysing agents (at 530-550 nm.)
  • FIG. 2 is a series of absorbance curves plotted versus time to demonstrate the time to chromogen formation and chromogen stability for various reagents, including the lysing reagent of the present invention.
  • FIG. 3 is another series of absorbance curves for various hemoglobin concentrations plotted against time to show reaction rates and stability for the selected current reference method.
  • FIG. 4 is a series of absorbance curves plotted against time to show reaction rates and stability for various concentrations of hemoglobin (same as in FIG. 3) using the method of the present invention.
  • FIG. 5 is a plot graph of a triphasic distribution of the subpopulations of white blood cells in a normal whole blood sample.
  • the present invention makes an ideal multipurpose lysing reagent for use in hemoglobin and leukocyte determinations on various instruments utilizing differing timing and reaction protocols.
  • the performance of this method is comparable to current methods utilized by Cell-Dyn® and Coulter Electronics instruments and commercially available lytic agents.
  • the multipurpose lysing reagent of the present invention has shown excellent stability against freezing and heating, and storage up to 15 months at 60° C. It also exhibits rapid reaction times (5-6 seconds to stabilize) and produces a chromogen absorbing at about 545 nm. The only necessary permutation is the optimization of the concentrations of reagents for particular instruments.
  • the present invention entails a solvent and at least one diluent and a lyse reagent.
  • the diluent is used to dilute a whole blood sample prior to hemoglobin and leukocyte determination.
  • the solvent is used to make the lyse reagent an aqueous solution before the lyse reagent contacts red blood cells in the diluted whole blood test sample.
  • the diluent is an inorganic or organic salt solution.
  • the solvent is typically deionized water.
  • the term diluent used hereinafter refers to a salt solution unless otherwise noted.
  • the lysing reagent of the present invention is comprised of an aqueous solution of one or more quaternary ammonium salts and hydroxylamine salts.
  • the lysing reagent is typically used in combination with a diluent. This combination of lysing reagent and diluent has been shown to be important for the reagent system to meet its specific requirement of hemoglobin and leukocyte determinations.
  • a selective buffer, and other ingredients, may be desirably added to the diluent to be used in combination with the lysing reagent in order to maintain the optimum overall solution pH and osmolality of the reagent system.
  • TTAB tetradecyltrimethyl ammonium bromide
  • the quaternary ammonium salts useful in the present invention are selected from the group of alkyl triethylammonium salts, alkyldimethylbenzylammonium salts and alkylpyridium salts consisting of: tetradecyltrimethyl ammonium bromide (TTAB), dodecyltrimethyl ammonium chloride, cetyltrimethyl ammonium bromide, hexadecyltrimethyl ammonium bromide, benzalkonium chloride, cetylpyridium chloride and other quaternary ammonium salts.
  • TTAB tetradecyltrimethyl ammonium bromide
  • dodecyltrimethyl ammonium chloride cetyltrimethyl ammonium bromide
  • cetyltrimethyl ammonium bromide hexadecyltrimethyl ammonium bromide
  • benzalkonium chloride cetylpyridium chloride and other quaternary ammonium salts.
  • the quaternary ammonium salt, or salts should be present in the lysing reagent at a total concentration range preferably between 0.1 and 20 % weight (wt.).
  • the specific concentration depends on the characteristics of the particular hematology system and on the operational procedure in which the reagent system is employed.
  • the hydroxylamine salt should be added to the lysing reagent to maintain a concentration preferably between 0.1 and 15 % (wt.).
  • the hydroxylamine salt is added to speed up the stabilization of the chromogen that is formed upon erythrolysis.
  • the specific concentration will be determined by the hematology system in which the lysing reagent is to be employed.
  • Buffers may also be used in the diluents.
  • the specifically preferred buffer depends on the particular hematology system in which the diluent is employed and the performance requirement of that instrument. Generally, the buffer will have a pKa between 6.2 and 8.0, a concentration between 5 and 25 millimolar (mM), pH of 6.5 to 7.5 and the buffer diluent has an osmolality between 250 and 350 milliosmoles/kilogram (mOsM/kg).
  • Some biological buffers employed in the present reagent system include N- 2-Acetamido!-2-iminodiacetic acid (ADA), 3- N-Morpholino!
  • a whole blood sample is treated with a diluent.
  • a lysing reagent is prepared by dissolving a specific quantity of quarternary ammonium salts and hydroxylamine salts in a solvent.
  • the lysing reagent is mixed with the diluted whole blood sample, and then the mixed sample is presented to a hemoglobin flow cell (absorbance spectrophotometer) for the measurement of optical density between 540 and 550 nanometers (nm).
  • the optical density measurements are then correlated to hemoglobin concentrations. The result is reported as a measured weight per volume of whole blood.
  • the lysing reagent is prepared by dissolving a specific quantity of quaternary ammonium salts and hydroxylamine salts in a solvent. Generally, the solvent used to dissolve the salts is deionized water.
  • Curve 1 corresponds to the cyanide-containing reference reagent (Cell-Dyn® Rapid Lyse, Abbott Laboratories, Abbott Park, Ill. 60064).
  • Curve 2 corresponds to the lysing reagent of the present invention.
  • Curve 3 represents data for the sodium dodecyl sulfate lyse of Oshiro et al.
  • Curve 4 was generated with data for the polycarboxylic acid with quaternary ammonium salt lysing reagent described in U.S. Pat. No. 4,185,964.
  • Curve 5 represents data from TTAB, a quaternary ammonium bromide alone in the reagent.
  • Curve 6 was generated with the reagent described in U.S. Pat. No. 5,250,437, with 0.5% sodium nitrite.
  • FIG. 1 illustrates that the lysing reagent of the present invention produces the desired absorbance characteristics between 530 and 550 nm.
  • FIG. 2 is a summary of experiments which were conducted to evaluate the reaction times (the conversion rate of hemoglobin at peak performance) and the stability of various prior art reagents and of the lysing reagent of the present invention at 540 nm. Reaction time is important to the performance of this reagent on hematology instruments especially in manual and semi-automated instruments. The timing of the readings in such instruments could affect the results.
  • FIG. 2 indicates that the lysing reagent of the present invention experiences rapid chromogen formation followed by very stable absorbance characteristics. Both of these characteristics were significantly better for the lysing reagent of the present invention than for the prior art cyanide-free reagents (curves 3, 4, 5 and 6). While the reference method with cyanide had a greater absorbance value, the cyanide-free reagent of the present method exhibits more rapid reaction time and greater chromogen stability.
  • FIG. 3 shows chromogen formation time and chromogen stability over time for blood samples with various hemoglobin concentrations (from bottom to top, 7.7 grams/deciliter (g/dL), 12.3 g/dL, 16.5 g/dL and 21.5 g/dL) with a reference lyse containing cyanide.
  • FIG. 4 shows chromogen formation time and chromogen stability over time for blood samples at these same hemoglobin concentrations, but instead using the lysing reagent of the present invention. A comparison of these two figures suggests that the reagent of the present invention demonstrates more rapid and more stable chromogen formation across the entire clinical range of hemoglobin concentrations in whole blood samples.
  • compositional ingredients of the diluents of the present invention are the compositional ingredients of the diluents of the present invention:
  • Triadine-10 a mixture of hexahydro-1,3,5-tris (2-hydroxyethyl)-s-triazine and sodium 2-pyridinethiol-1-oxide.
  • compositional examples of the lysing reagent of the present invention are the compositional examples of the lysing reagent of the present invention.
  • Example 1 For Examples 1-18, and 20 the diluent used was Diluent No. 2. In Example 19 the diluent used was Diluent No. 1. Example 21 utilized Diluent No. 3. In all the Examples except as otherwise noted, thirty (30) microliters ( ⁇ L) of whole blood was prediluted with 7.5 milliliters (mL) of diluent to give a 1:250 dilution. One (1) mL of a multipurpose lysing reagent was added to the diluted whole blood sample.
  • Salts such as sodium chloride (NaCl), potassium chloride (KCl) and the like may be added to increase the conductivity of the liquid reagents utilized in instruments.
  • the increased conductivity can be used for sensor detection of low liquid levels in reagent containers.
  • a multipurpose lysing reagent was prepared by dissolving 20 grams (g) of hydroxylamine hydrochloride (Sigma, St. Louis, Mo., 63178), 37.5 g of benzalkonium chloride (Amresco, Solon, Ohio, 44139) and 37.5 g dodecyltrimethyl ammonium chloride (Sigma) in 1 liter of deionized water. Alternatively, 42.5 g of benzalkonium chloride and 42.5 g of dodecyltrimethyl ammonium chloride can be used. The results displayed in Table 1 utilize 37.5 g of both quarternary ammonium salts in the aqueous lyse reagent.
  • This lysing reagent can be used in the Cell-Dyn® 1300, 1600 and 3500 instruments.
  • a serial concentration of whole blood was analyzed for hemoglobin content in the Abbott Diagnostics Cell-Dyn® Model 1600 according to the standard operating procedures to investigate the correlation of the results obtained with the cyanide-containing reference lyse (Cell-Dyn® Rapid Lyse) and with the multipurpose (CN-free) lysing reagent of the present invention. Data are presented in Table 1.
  • the reported hemoglobin values are the mean of two assays for prepared fresh blood.
  • Example 2 Using the experimental lysing reagent prepared in Example 1, a serial concentration of prepared whole blood was analyzed for white blood cell counts (WBC) in the Cell-Dyn® 1600 instrument with the reference lyse (Cell-Dyn® Rapid Lyse) and the experimental lyse.
  • the WBC results are reported in Table 2.
  • the reported hemoglobin values are the mean of two assays for prepared fresh blood.
  • Example 2 An experimental lysing reagent prepared according to the formulation set forth in Example 1 was used to compare the reproducibility of the experimental lyse versus the Cell-Dyn® Rapid Lyse used as a reference lyse. Three fresh blood samples were analyzed with the two lysing reagents on the Cell-Dyn® 1600 instrument. The results are set out below in Tables 3 and 4. Table 5 shows good correlation between two lyse reagents for Hb and WBC determinations.
  • Diluent No. 1 was used to dilute the whole blood samples.
  • Lysing agents for use in the Cell-Dyn® 900 instrument were made by adding to 10 mL of deionized water. The formulations are listed in Table 21. Stability results of lyse reagent formulation #4 as compared to the reference lyse are shown in Table 22. The results of the experimental multipurpose lyse of the present invention was comparable to the reference lyse.
  • Lysing reagents formulations for use in the Cell-Dyn® 610, 1400, 1500, 1600, and 2000 instruments were made by adding to 1000 mL of deionized water the components listed in Table 23. Stability results of the lyse reagent formulation #7 as compared to the reference lyse are shown in Table 24. In addition, the formulation of lyse reagent #7 in Table 23 produced the cyanide free differential plot graph of FIG. 5.
  • Lysing reagent for use in the Cell-Dyn® 3000 instrument was made by adding to 1000 mL of deionized water 10 g of benzalkonium chloride (50%), 10 g of dodecyltrimethyl ammonium chloride (50%), 2.35 g hydroxylamine hydrochloride and 4.5 g NaCl.* Stability results of the lyse reagent formulation compared to the reference lyse is shown in Table 25.
  • the results of the experimental multipurpose lyse of the present invention has comparable performance as the reference lyse.
  • 20 g of benzalkonium chloride (50%), 20 g of dodecyltrimethyl ammonium chloride (50%), 4.7 g hydroxylamine hydrochloride and 9.0 g NaCl can be used.

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US08/863,827 1994-07-14 1997-05-27 Methods and reagents for cyanide-free determination of hemoglobin and leukocytes in whole blood Expired - Lifetime US5958781A (en)

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Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6114130A (en) * 1998-08-04 2000-09-05 Abx Reagent for measurement of the haemoglobin and determination of the leukocytes in a blood sample
US20040048386A1 (en) * 2002-04-05 2004-03-11 Streck Laboratories Inc. Method of using cyanide-free lyse solution to emulate a cyanide-containing lyse solution in the measurement of hemoglobin
WO2006042555A3 (fr) * 2004-10-20 2006-06-01 Chempaq As Reactif lysogene permettant le recensement simultane de differents types de cellules sanguines dans un echantillon sanguin
FR2883972A1 (fr) * 2005-03-31 2006-10-06 C2 Diagnostics Sa Procede pour l'analyse d'un echantillon de sang et appareil et reactif pour sa mise en oeuvre
US20060263889A1 (en) * 2005-05-04 2006-11-23 Beckman Coulter, Inc. Cyanide-free lytic reagent composition and method of use for hemoglobin and white blood cell measurement
US20080153170A1 (en) * 2006-12-22 2008-06-26 Garrett Diana G Method for determination of nucleated red blood cells and leukocytes in a whole blood sample in an automated hematology analyzer
FR2931557A1 (fr) * 2008-05-20 2009-11-27 Biocode Hycel France Sa Procede de determination du taux d'hemoglobine, de numeration et de differenciation des globules blancs et milieu adapte
US20110053206A1 (en) * 2009-08-26 2011-03-03 Abbott Laboratories Method of using ligand-free lysing agent in hemoglobin analysis
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US20040048386A1 (en) * 2002-04-05 2004-03-11 Streck Laboratories Inc. Method of using cyanide-free lyse solution to emulate a cyanide-containing lyse solution in the measurement of hemoglobin
US6890756B2 (en) 2002-04-05 2005-05-10 Streck Laboratories, Inc. Method of using cyanide-free lyse solution to emulate a cyanide-containing lyse solution in the measurement of hemoglobin
US20080085560A1 (en) * 2004-10-20 2008-04-10 Bjorn Ekberg Lysing Reagent For Simultaneous Enumeration Of Different Types Of Blood Cells In A Blood Sample
WO2006042555A3 (fr) * 2004-10-20 2006-06-01 Chempaq As Reactif lysogene permettant le recensement simultane de differents types de cellules sanguines dans un echantillon sanguin
FR2883972A1 (fr) * 2005-03-31 2006-10-06 C2 Diagnostics Sa Procede pour l'analyse d'un echantillon de sang et appareil et reactif pour sa mise en oeuvre
US20090142744A1 (en) * 2005-03-31 2009-06-04 C2 Diagnostics Method for the Analysis of a Blood Sample, and Apparatus and Reagent for Its Implementation
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US7981681B2 (en) 2005-03-31 2011-07-19 C2 Diagnostics Method for the analysis of a blood sample, and apparatus and reagent for its implementation
WO2006103334A3 (fr) * 2005-03-31 2007-03-01 C2 Diagnostics Procede pour l'analyse d'un echantillon de sang et appareil et reactif pour sa mise en oeuvre
EP1877802A4 (fr) * 2005-05-04 2008-06-18 Beckman Coulter Inc Composition reactive lytique exempte de cyanure et procede d'utilisation de cette composition pour le dosage de l'hemoglobine et des leucocytes
US20060263889A1 (en) * 2005-05-04 2006-11-23 Beckman Coulter, Inc. Cyanide-free lytic reagent composition and method of use for hemoglobin and white blood cell measurement
US7235404B2 (en) * 2005-05-04 2007-06-26 Beckman Coulter, Inc. Cyanide-free lytic reagent composition and method of use for hemoglobin and white blood cell measurement
US20080153170A1 (en) * 2006-12-22 2008-06-26 Garrett Diana G Method for determination of nucleated red blood cells and leukocytes in a whole blood sample in an automated hematology analyzer
US7674622B2 (en) * 2006-12-22 2010-03-09 Abbott Laboratories, Inc. Method for determination of nucleated red blood cells and leukocytes in a whole blood sample in an automated hematology analyzer
FR2931557A1 (fr) * 2008-05-20 2009-11-27 Biocode Hycel France Sa Procede de determination du taux d'hemoglobine, de numeration et de differenciation des globules blancs et milieu adapte
WO2009150327A3 (fr) * 2008-05-20 2010-03-25 Biocode Hycel France Sa Procede de determination du taux d'hemoglobine, de numeration et de differenciation des globules blancs et milieu adapte
US20110053206A1 (en) * 2009-08-26 2011-03-03 Abbott Laboratories Method of using ligand-free lysing agent in hemoglobin analysis
US8614066B2 (en) 2009-08-26 2013-12-24 Abbott Laboratories Method of using ligand-free lysing agent in hemoglobin analysis
WO2011025711A1 (fr) 2009-08-26 2011-03-03 Abbott Laboratories Procédé d'utilisation d'agent de lyse sans ligand dans l'analyse d'hémoglobine
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JPH10503016A (ja) 1998-03-17
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WO1996002841A1 (fr) 1996-02-01
US6740527B1 (en) 2004-05-25
JP3529786B2 (ja) 2004-05-24

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